The objective of this research project is to assess the factors responsible for differences in the substrate specificities among cytochrome P-450-dependent microsomal mixed-function oxidase systems (MFO) from various sources. Present work involves the purification of cytochrome P-450, NADPH-cytochrome c reductase, and lipid fractions from rabbit pulmonary and hepatic microsomes. The cytochrome P-450s are being examined by UV-visible spectroscopy, electron paramagnetic resonance spectroscopy, SDS-gel electrophoresis, and by activities in reconstituted systems. The long-range objective of this work is to determine the influence of: 1) multiple forms of the enzymic components of the MFO system; 2) endogenous compounds; and 3) exogenous compounds (inhibitors and inducers) on the substrate specificities of MFO systems from different tissues and species. BIBLIOGRAPHIC REFERENCES: Philpot, R.M. and Arinc, E.: Separation and purification of two forms of hepatic cytochrome P-450 from untreated rabbits. Molec. Pharmacol. 12: 483-493, 1976. Arinc, E. and Philpot, R.M.: Preparation and properties of partially purified pulmonary cytochrome P-450 from rabbits. J. Biol. Chem. 21: 3213-3220, 1976.